Influenza, an illness caused by respiratory infection with influenza viruses, often occurs in winter. It is known to have very high infectivity and to affect all age groups, particularly elderly people (Treanor J, 2004, N Engl J Med. 350(3):218-20). Influenza viruses are enveloped RNA (ribonucleic acid) viruses belonging to the family Orthomyxoviridae and have a genome composed of eight negative-sense, single-stranded RNA (ribonucleic acid) segments. These influenza viruses are classified into types A, B and C. Influenza A viruses are further divided into subtypes based on their major surface proteins hemagglutinin (HA) and neuraminidase (NA). Up to date, 17 HAs and 10 NAs have been identified (Cheung T K and Poon L L 2007, Ann N Y Acad. Sci. 1102:1-25; Tong S, et al. 2012, Proc. Natl. Acad. Sci. U.S.A. 109:4269-4274). Influenza viruses can affect birds, pigs and humans depending on their types and have a genome composed of RNA segments, and for this reason, their genes can continuously mutate and recombine, resulting in new genetic variations (Treanor J, 2004. N Engl J Med. 350(3):218-20). Due to this continuous mutation, it is difficult to obtain permanent immunity against influenza viruses, and thus a preventive method that is currently thought to be most effective is a method of administering a vaccine against a particular type of influenza virus expected to be prevalent each year to develop immunity against the influenza virus each year.
Influenza virus vaccines that are currently administered each year are trivalent vaccines containing influenza A H1, H3 subtype HA and influenza type B HA.
Vaccines against influenza viruses are generally produced using eggs, but this production method is a time-consuming and inefficient method. Accordingly, this method has a problem in that it is difficult to produce sufficient amounts of vaccines each year within a limited time frame. In an attempt to solve this problem, studies on methods of producing vaccines by cell culture have been actively conducted by several pharmaceutical companies (GSK, Baxter, etc.). In addition, if pandemic influenza virus infection occurs, it is very difficult to develop a vaccine against the infection within a short time. Also, antiviral drugs are not completely reliable due to a problem associated with the emergence of drug-resistant mutant viruses.
To overcome this problem, antibodies against influenza viruses have recently been actively developed (Throsby et al, 2008, PloS One 3 (e3942); Sui et al., 2009, Nature structural & molecular biology. 16 (265-273); Simmons et al, 2007, PloS Medicine 4 (e178); Wrammert et al., 2011, J Exp Med. 208 (181-193); Corti et al., 2011, Science 333 (850-856)).
Blood products from recovered patients have been used to treat patients infected with various viruses, as well as to treat pandemic flu infections. For example, when patients infected with Spanish influenza virus had symptoms of pneumonia, blood products collected from patients who recovered from infection with the influenza virus are used to treat the influenza virus (Luke et al., 2006. Annals of internal medicine. 145:599). As such, hyperimmune globulin (IgIv) is purified from human plasma and used to treat patients infected with various viruses, but the product obtained as described above may not be safe from potential infectious agents in blood and is inefficient for mass production.
Antibodies against influenza A virus, which were recently filed for patent protection by the applicant, showed neutralizing activity against various influenza subtypes. Particularly, an antibody disclosed in Korean Patent Application No. 10-2011-0020061 showed neutralizing activity, mainly against phylogenetic group 1 (H1, H2, H5 and H9), and an antibody disclosed in Korean Patent Application 10-2012-0107512 showed neutralizing activity, mainly against phylogenetic group 2 (H3 and H7). Accordingly, the present inventors have conducted studies to develop a cocktail formulation containing at least two kinds of antibodies, which can exhibit preventive and therapeutic effects against all viruses belonging to groups 1 and 2, which are likely to be pandemic.